Microbiome and metabolome changes after fecal microbiota, live-jslm, administration are associated with health-related quality of life improvements

IF 3.1 3区生物学 Q3 MICROBIOLOGY

Anaerobe Pub Date : 2025-12-01 Epub Date: 2025-10-18 DOI:10.1016/j.anaerobe.2025.103006

Rohan Mishra , Adam Harvey , Amy Guo , Glenn Tillotson , Paul Feuerstadt , Sahil Khanna , William D. Shannon , Ken F. Blount

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引用次数: 0

Abstract

Objectives

Increasing evidence indicates a gut microbiome-brain axis, but more robust statistical methods are needed to solidify this connection. In a large phase 3, randomized, placebo-controlled clinical trial (PUNCH CD3; NCT03244644), fecal microbiota, live-jslm (REBYOTA; RBL, previously RBX2660), was effective in preventing recurrent Clostridium difficile infections, and trial participants had significant gut microbiome and metabolome shifts concurrent with significant changes in health-related quality of life (HRQOL). Advanced statistical methods were applied to data from this trial to further explore and demonstrate associations between changing HRQOL and microbiome or metabolome changes.

Methods

A categorical statistical analysis queried whether patient-reported Cdiff32 HRQOL scores were more likely to improve after RBL than after placebo among PUNCH CD3 participants, and a Dirichlet-multinominal recursive partitioning model assessed whether mental domain Cdiff32 HRQOL scores were linked to participants’ fecal microbiome or bile acid compositions.

Results

Cdiff32 mental domain HRQOL scores were more likely to be improved after RBL administration compared with placebo among treatment responders. Cdiff32 mental domain scores were associated with changing gut microbiome and metabolome compositions, with a gradient of increased Clostridia and Bacteroidia and increased secondary bile acid predominance associated with better Cdiff32 scores.

Conclusions

The microbiota-gut-brain axis is posited to modulate health-related quality of life, microbiome, and metabolome changes through immune, gastrointestinal, and central nervous system functions in patients with recurrent C. difficile infection following RBL administration. These analyses provide a novel approach for investigating multi-omics data and categorical health-related quality of life questionnaires and generate new insights for further clinical studies.

Clinical trial registration

NCT03244644.

查看原文本刊更多论文

粪便微生物群、活体jslm、给药后的微生物组和代谢组变化与健康相关的生活质量改善有关。

目的：越来越多的证据表明肠道微生物组-脑轴，但需要更强大的统计方法来巩固这种联系。在一项大型3期随机安慰剂对照临床试验（PUNCH CD3; NCT03244644）中，粪便微生物群live-jslm （REBYOTA； RBL，以前的RBX2660）可有效预防复发性艰难梭菌感染，试验参与者的肠道微生物群和代谢组发生显著变化，同时健康相关生活质量（HRQOL）发生显著变化。我们采用先进的统计学方法对该试验的数据进行分析，以进一步探索和证明HRQOL变化与微生物组或代谢组变化之间的关联。方法：通过分类统计分析，询问在PUNCH CD3参与者中，患者报告的Cdiff32 HRQOL评分在RBL后是否比安慰剂后更有可能改善，并使用dirichlet多项递归划分模型评估心理域Cdiff32 HRQOL评分是否与参与者的粪便微生物组或胆胆酸组成有关。结果：在治疗应答者中，与安慰剂相比，服用RBL后Cdiff32心理域HRQOL评分更有可能得到改善。Cdiff32心理结构域评分与肠道微生物组和代谢组组成的变化有关，梭状芽孢杆菌和拟杆菌的梯度增加以及次级胆汁酸优势的增加与Cdiff32评分较高相关。结论：微生物-肠-脑轴被认为可以通过免疫、胃肠道和中枢神经系统功能调节艰难梭菌复发感染患者在RBL治疗后健康相关的生活质量、微生物组和代谢组的变化。这些分析为研究多组学数据和分类健康相关生活质量问卷提供了一种新的方法，并为进一步的临床研究提供了新的见解。临床试验注册：NCT03244644。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anaerobe 生物-微生物学

CiteScore

5.20

自引率

8.70%

发文量

137

审稿时长

76 days

期刊介绍： Anaerobe is essential reading for those who wish to remain at the forefront of discoveries relating to life processes of strictly anaerobes. The journal is multi-disciplinary, and provides a unique forum for those investigating anaerobic organisms that cause infections in humans and animals, as well as anaerobes that play roles in microbiomes or environmental processes. Anaerobe publishes reviews, mini reviews, original research articles, notes and case reports. Relevant topics fall into the broad categories of anaerobes in human and animal diseases, anaerobes in the microbiome, anaerobes in the environment, diagnosis of anaerobes in clinical microbiology laboratories, molecular biology, genetics, pathogenesis, toxins and antibiotic susceptibility of anaerobic bacteria.